Tissue Conditions and the

Transcription

1 Management of Oral Soft Tissue Conditions and the Use of Medications 29 August 2017 Mike Brennan DDS, MHS Department of Oral Medicine Carolinas Medical Center Charlotte, NC

2 Objectives Differential diagnosis of soft tissue conditions Describe more common soft tissue conditions Diagnosis of soft tissue conditions Management strategies of mucosal lesions Treatment Prevention

3 Differential Diagnosis-NIRDS Neoplastic Infectious Reactive Developmental Systemic

4 NEOPLASTIC

5 Leukoplakia- White Clinical diagnosis only Histologically: hyperplasia, mild, moderate, or severe dysplasia, carcinoma in-situ, invasive carcinoma Thin leukoplakia: seldom malignant change Thick leukoplakia: 1-7% malignant change Granular or verruciform: 4-15% malignant change Erythroleukoplakia: 28% malignant change

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7 Neoplastic: Red Lesions SCCA

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9 Diagnosis: Incisional vs. Excisional Biopsies

10 Dysplasia Management Medical Systematic Review: 9 studies met criteria for low bias in prior review Three studies were reviewed based adequate study quality. topical bleomycin systemic retinoids systemic lycopene No therapeutic recommendations for bleomycin and cis-retinoic acid Lycopene (4 and 8 mg) may have some efficacy in patients with risk factors similar to those found in a subcontinental Indian population, for the shortterm resolution of oral epithelial dysplasia

11 Dysplasia Management Surgical Lack RCTs that would allow to assess the effectiveness of surgical treatment, including lasers In non-rcts the effectiveness of various surgical modalities in preventing malignant transformation of oral dysplasia have resulted in contradictory outcomes

12 INFECTIOUS

13 Candidiasis Psuedomembranous Erythematous Hyperplastic Angular cheilitis

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21 Soft tissue diagnostic tests Fungal Superficial: Smear potassium hydroxide or stained with PAS hyphae Culture Deep fungal: Biopsy

22 Treatment - Fungal Topical 10 mg clotrimazole troches 5x/d for 7-10 days Nystatin rinse- 100,000U/mL swish and spit 5mL 4x/d for 2 weeks Chlorhexidine rinse 10 ml bid Probiotics (reduced oral candida in elderly population- RCT J Dent Res x2) Nystatin/triamcinolone cream- dab on corners of mouth 4x/d Clotrimazole-betamethasone dipropionate (Lotrisone) cream Miconazole (Monistat 7) nitrate vaginal cream 2% Nystatin ointment (thin layer on denture) tid

23 Treatment - Fungal Systemic Fluconazole 200 mg day 1 followed by 100 mg/d 1-2 weeks Ketoconazole 200 mg/day for 14 days Both are potent inhibitors of cytochrome P- 450: Check Pharmacology Reference- Drugs.com: 149 major drug interactions- Warfarin, Xanax, Lipitor, Plavix, hydrocodone

24 Infectious: Red Lesions Fungal Erythematous candidiasis Immunocompromised Histoplasmosis, Coccidioidomycosis, Blastomycosis, Cryptococcus (Solitary painful ulceration of tongue, palate, buccal mucosa) Aspergillosis (sinus, after tooth extraction or endodontic treatment) Mucormycosis (Maxillary sinus infection, swelling of alveolar process and/or palate) Extensive tissue destruction due to preference for small blood vessels: infarction and necrosis disrupts blood flow

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26 Infectious: Red Lesions Viral HSV HSV-1 vs. HSV-2 Children: Acute herpetic gingivostomatitis-both moveable and attached mucosa Adults: Pharyngotonsillitis- vesicles tonsils and posterior pharynx. Oral mucosa anterior to waldeyer s ring <10% of cases. Most common recurrent site: lip (herpes labialis)

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30 Soft tissue diagnostic tests Viral Culture 2-4 days for + ID Cytology Virally damaged epithelial cells Serology Rising titre of antibody DNA in situ hybridization for specific virus identification Bacterial Aerobic and anaerobic culture

31 Infectious: Red Lesions Viral VZV Primary infection: chickenpox (oral lesion: palate and buccal mucosa most frequently involved: vesicles. Recurrence: Herpes Zoster 10-20% of older population. One dermatome affected Prodromal pain, fever, malaise 1-4 days before cutaneous/oral lesions.

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34 Treatment- Viral Observe/supportive care Immunocompetent patient Maintain hydration and nutrition Topical MBX- care with lidocaine (esp. children and elderly) Aquaoral with SPF Penciclovir (Denavir) cream 1% Docosanol (Abreva)

35 Treatment - Viral Systemic Acyclovir caps 200 mg: 2 caps 3x/day for 7 days Valacyclovir 500 mg: 1 g 2x/day for 7-10 days (initial episode) Valacyclovir 500 mg: 4 caps when prodromal symptoms start Valacyclovir 500 mg: 1 cap 2x/day for 3 days

36 Prevention - Viral Systemic Acyclovir caps 200 mg: 2 caps 2x/day Valacyclovir 500 mg: 1 cap daily

37 REACTIVE

38 Reactive-White

39 Reactive lesions Focal (frictional) hyperkeratosis Response to low-grade irritation (sharp edge) Buccal mucosa along occlusal line No dysplastic changes

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41 Reactive lesions Tobacco pouch keratosis Muccobuccal fold, granular to wrinkled appearance Gingival, periodontal destruction possible 15% chewing tobacco, 60% snuff users Malignant potential Nicotine stomatitis Palatal mucosa: elevated papules with red centers are inflammed minor ducts Not pre-malignant. May revert when discontinues smoking

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44 Reactive-Red

45 Reactive: Red Lesion Aphthae Unknown etiology, incidence 20-60% 3 Clinical forms (minor, major, herpetiform) Non-keratinized mucosa Diagnosis by elimination Rule out allergies, hematologic abnormalities, infectious agents, nutritional imbalances, trauma, stress.

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47 Management/prevention of RAS Clobetasol (0.05% gel) on lesion immediately when first symptoms occur Chlorhexidine start 1-2x/day for 2 weeks and decrease to every other day or every 3 rd day Vitamin B12 supplement Alteration of diet?

48 Topical steroid by strength Ultrapotent Clobetasol 0.05% Halobetasol 0.05% Potent Dexamethasone 0.5 mg/5 ml Fluocinonide 0.05% Intermediate: Triamcinolone acetonide (Kenalog) 0.1% Low: Hydrocortisone 1% Gel, Ointment, Cream, Compounded

49 Topical Steroids for external use only High cost Atrophy of mucosa Fungal side effects

50 Topical Steroids and Fungal Infection: Study Objectives Primary Determine the incidence of oral candidiasis in patients treated with topical steroids for oral lichen planus (OLP) Secondary Determine if different antifungal therapies are more effective than others in preventing the development of clinical fungal infections Marable DR, Bowers LM, Stout T, Stewart CM, Berg KM, Sankar VS, DeRossi SS, Thoppay JR, Brennan MT. Oral candidiasis following steroid therapy for oral lichen planus. Oral Dis Mar;22(2):140-7.

51 Methods Multicenter, retrospective chart review of a well-characterized group of Lichen Planus patients Carolinas Medical Center (CMC) University of Florida College of Dentistry (UF) University of Texas Health Science Center at San Antonio (UTHSCSA) Georgia Regents University College of Dental Medicine (GRU) 51

52 Methods Inclusion Criteria Patients diagnosed with clinical oral lichen planus. Patients at CMC, UF, UTHSCSA, and GRU Patients treated for lichen planus with topical steroids for at least 2 weeks AND a follow-up visit within 5 weeks of the initiation of daily topical steroids. 52

53 Methods Treatment regimen for oral lichen planus Topical Steroid Used: Y/N Generic name and % of topical steroid Systemic Steroid Used: Y/N Antifungal Preventive Therapy Used: Y/N Generic name and % (if applicable) of antifungal therapy 53

54 Methods Follow-up Data Clinical appearance: Improved/Worsening/No change Clinical symptoms (burning/pain): Improved/Worsening/No change Oral Fungal Infection? Y/N If yes, describe appearance Treatment of oral fungal infection 54

55 Results Topical steroids were used in 303 (96.2%) patients. Systemic steroids were used in 12 (3.8%). % patients 55

56 Results Objective improvement Clobetasol 91.1% with clobetasol 81.5% without clobetasol (p=0.02) Use of any preventive antifungal 90.6% with antifungal 80.5% without antifungal (p=0.02) Subjective improvement Clotrimazole 94.3% with clotrimazole 85.4% without clotrimazole (p=0.04)

57 Results Oral fungal infections at follow-up Total: 43 (13.7%) patients No significant difference between sites (p=0.36). CMC - 24/155 (15.5%) UF - 11/67 (16.4%) UTHSCSA - 6/59 (10.2%) GRU - 2/34 (5.9%) 57

58 Results Fungal infections at follow-up, by steroid treatment Clobetasol - 32/183 (17.5%), (p=0.02) Dexamethasone - 11/98 (11.2%), (p=0.39) Fluocinonide - 1/22 (4.6%), (p=0.33) Lotrisone - 4/20 (20%), (p=0.50) Preventive antimycotic agents were used in 203 patients and no antimycotic in 111, with fungal infections occurring in 29 (14.3%) and 14 (12.6%), respectively. 58

59 Results Salivary flow testing was completed in 51 patients of which 10 developed OFI. Low stimulated salivary flow group ( 0.7 ml/min) 9 (90%) OFI patients High stimulated salivary flow (>0.7 ml/min) 1 (10%) OFI patient No difference in unstimulated flow 59

60 Conclusions The incidence of oral fungal infections in OLP patients following steroid therapy was higher than anticipated (13.7%). Clobetasol had a significantly higher incidence of fungal infection compared to all other steroid therapies. Low saliva is a major risk factor for a fungal infection 60

61 Reactive: Red Lesion Allergic reaction to systemic drugs Erythema multiforme Lichenoid Lupus erythematous-like eruptions Pemphigus-like lesions

62 Reactive: Red Lesion Erythema Multiforme Immunologically mediated 50% of cases preceding infection or exposure to drug Oral: erythematous patches that develop shallow erosions and ulcerations. Target skin lesions in 50% of cases More severe: erythema multiforme major (Stevens-Johnson syndrome) and Toxic Epidermal Necrolysis (Drug involved)

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64 Management Erythema Multiforme Prednisone start of lesions Preventive: Acyclovir 400 mg 2x/day Valacyclovir mg /day

65 DEVELOPMENTAL- White

66 Hereditary conditions Leukoedema Natural variant. Asymptomatic, symmetric gray-white, filmy or milky surface Stretching removes clinical appearance More frequent in African Americans

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68 Fordyce granules Sebaceous glands that occur on the oral mucosa. Normal variant Found in up to 80% of the population Multiple yellowish-white papular lesions. Most common buccal mucosa.

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70 Developmental: Red Lesion Benign Migratory Glossitis (Geographic Tongue) Red Lesion with white border Usually asymptomatic Moves Diagnosis Elimination Rule out fungal etiology of symptoms

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72 Management of Benign Migratory Glossitis Topical Steroids Antifungals Rule out hematinic deficiencies

73 SYSTEMIC

74 Lichen Planus The reported prevalence rates of oral lichen planus (OLP) vary from 0.5% to 2.2% of the population Often develops between years, and it is more frequently seen in women Intra-oral: Reticular, plaque-like, erosive, bullous forms, desquamative Extra-oral: PPPP: purple, polygonal, pruritic papules- Flexural surfaces, scalp, nails, genitals Etiology unknown Lichenoid reactions (drugs, amalgam, gold)

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79 Treatment for symptomatic OLP- systematic review Topical corticosteroids (+/- topical anti-mycotics) are the first-line treatment for localized lesions Insufficient evidence regarding different dosages, formulations or modes of delivery of topical steroids (eg. paste, spray, mouthwash) to make an evidence based recommendation about which is best Systemic corticosteroids (+/- topical anti-mycotics) are the first-line treatment only for severe, wide-spread OLP and for lichen planus involving other muco-cutaneous sites (eg.: vaginal/vulval LP) recalcitrant /resistant to topical therapies Topical retinoids should be considered only as second line therapy for OLP; systemic retinoids are not recommended Topical calcineurin-inhibitors should be considered only as second-line therapy.

80 Management Lichen Planus Topical steroids Up to 2 weeks followed by 1 week break: repeat if needed Concern of atrophy of mucosa and adrenal suppression with long-term use Optimize oral care Chlorhexidine with poor plaque control Tacrolimus (protopic) 0.1% ointment No a steroid BUT- black box warning

81 LP malignant transformation The alleged annual malignant transformation rate for OLP is between 0.2% and 0.5% 10-50X increased risk of SCCA 2-4 /100 patients over 10 year follow up Patients should be encouraged to avoid or discontinue habits such as excessive tobacco and alcohol use, that are likely to increase the risk of malignant transformation Long-term monitoring may be problematic as this is resource intensive. At a minimum, annual monitoring of OLP is recommended

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83 Oral Lichenoid Reactions Oral lichenoid contact lesions (OLCL s) are seen in direct topographic relationship to an offending agent This reaction is most often attributable to dental restorative materials, most commonly amalgam With the removal and replacement of the putative causative material, the majority of such OLCL s resolve within several months Patch testing?

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85 Lupus Oral lesions approximately 25% of SLE. May appear lichenoid, ulcerative or granulomatous. May have more erosive quality.

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88 Pemphigus Autoantibodies to desmosomes 50% have oral mucosal lesions prior to mucocutaneous lesions. Eventually all have intra-oral lesions. Prior to corticosteroids, 60-80% mortality

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90 Pemphigoid Autoantibodies to basement membrane Average age 60 Oral lesions most patients. Begin as vesicles or bullae. Painful and persistent if untreated. Ocular lesions in 25% of pemphigoid patients with oral lesions

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92 Management - Pemphigoid Avoid hard/sharp foods Optimal plaque control Chlorhexidine Topical steroids Doxycycline 100 mg daily long-term Refractory: dapsone, prednisone

93 Gingival Differential Desquamative Gingivitis Erosive LP (71%) Pemphigoid (14%) Pemphigus (13%) Linear IgA Disease Epidermolysis Bullosa Acquisita Plasma Cell Gingivitis Mass on Gingiva (4 Ps) Pyogenic Granuloma Peripheral Ossifying Fibroma Peripheral Giant Cell Granuloma Parulis

94 White Lesions Does lesion rub away? Yes No Infections Etiology Pseudomembranous candidiasis Secondary syphilis Diphtheria Reactive Etiology Thermal or chemical burn Allergy Mechanical trauma Keratosis Hereditary Frictional Smoker s Lichen Planus/ Lichenoid Reaction Lupus Erythematosus Infections etiology Hairy leukoplakia Fungal Dysplastic Tissue changes Mild, moderate, severe dysplasia Carcinoma in situ Squamous cell carcinoma

95 Erythematous Lesions Generalized? Yes No Dermatosis erosive lichen planus pemphigoid pemphigus epidermolysis bullosa acquisita psoriasis Nutritional Deficiency ferritin folate vitamin B12 Fungal Etiology Center of tongue: Median rhomboid glossitis Glossitis Palate: -Denture stomatitis -Fungal Bilateral corners of mouth: Angular cheilitis Fungal; candidosis Staph or strep Hematinic deficiency Oral Crohn s disease Immuno compromised state (e.g. Diabetes, HIV) Gingival: Plaque-associated gingivitis Dermatosis Allergy (plasma cell gingivitis) Dysplastic Tissue changes (solitary lesion) Mild, moderate, severe dysplasia Carcinoma in situ Squamous cell carcinoma

96 Management of Oral Lesions Acute lesions (i.e. < 2 weeks) Chronic lesions (> 2 weeks) Long term follow-up of chronic oral lesions Transformation of oral lesions to oral cancer

97 Management of Acute Lesions New onset lesions CHLORIDE Head and neck examination Evaluate for etiologic factors Social habit Change in medication or oral care product Parafunctional habits Trauma- sharp areas NIRDS

98 Management of Acute Lesions Eliminate potential etiologic factors Treat with antifungals if on differential Chlorhexidine 2x/day for 2 weeks Clotrimazole troches 10 mg 5x/d for 7-10 days Nystatin/triamcinolone cream dab corners of mouth 4x/d Probiotic yogurt Fluconazole 200 mg day 1 followed by 100 mg/d one week Nystatin ointment (thin layer on denture) tid Return for reassessment in 2 weeks Consider incisional biopsy for definitive diagnosis

99 Questions? Carolinas Center for Oral Health Carolinas Medical Center 1601 Abbey Place, Suite 220 Charlotte, NC Office number: